Variant chrX-52815151-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001386970.1(XAGE5):c.238G>A(p.Gly80Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000926 in 1,209,425 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.000077 ( 0 hom. 25 hem. )

Consequence

XAGE5
NM_001386970.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0940

Variant links:

Genes affected

XAGE5 (HGNC:30930): (X antigen family member 5) This gene is a member of the XAGE subfamily, which belongs to the GAGE family. The GAGE genes are expressed in a variety of tumors and in some fetal and reproductive tissues. The protein encoded by this gene shares a sequence similarity with other GAGE/PAGE proteins. Because of the expression pattern and the sequence similarity, this protein also belongs to a family of CT (cancer-testis) antigens. [provided by RefSeq, Jul 2008]

XAGE5 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021777302).

BS2

High Hemizygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
XAGE5	NM_001386970.1 linkuse as main transcript	c.238G>A	p.Gly80Arg	missense_variant	5/6	ENST00000375501.2	NP_001373899.1
XAGE5	NM_130775.3 linkuse as main transcript	c.238G>A	p.Gly80Arg	missense_variant	4/5		NP_570131.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
XAGE5	ENST00000375501.2 linkuse as main transcript	c.238G>A	p.Gly80Arg	missense_variant	5/6	5	NM_001386970.1	ENSP00000364651	P1
XAGE5	ENST00000375503.7 linkuse as main transcript	c.*166G>A		3_prime_UTR_variant, NMD_transcript_variant	4/5	1		ENSP00000364653
XAGE5	ENST00000445860.2 linkuse as main transcript	n.241G>A		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes

AF:

0.000241

AC:

AN:

112057

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

34235

show subpopulations

Gnomad AFR

AF:

0.000812

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000224

AC:

AN:

182800

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

67400

show subpopulations

Gnomad AFR exome

AF:

0.000913

Gnomad AMR exome

AF:

0.000256

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000846

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000490

Gnomad OTH exome

AF:

0.000443

GnomAD4 exome

AF:

0.0000775

AC:

AN:

1097313

Hom.:

Cov.:

AF XY:

0.0000689

AC XY:

AN XY:

362809

show subpopulations

Gnomad4 AFR exome

AF:

0.000872

Gnomad4 AMR exome

AF:

0.000370

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000574

Gnomad4 FIN exome

AF:

0.0000247

Gnomad4 NFE exome

AF:

0.00000951

Gnomad4 OTH exome

AF:

0.000130

GnomAD4 genome

AF:

0.000241

AC:

AN:

112112

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

34300

show subpopulations

Gnomad4 AFR

AF:

0.000810

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000136

Hom.:

Bravo

AF:

0.000295

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000239

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.238G>A (p.G80R) alteration is located in exon 4 (coding exon 3) of the XAGE5 gene. This alteration results from a G to A substitution at nucleotide position 238, causing the glycine (G) at amino acid position 80 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.5

DANN

Benign

0.46

DEOGEN2

Benign

0.029

T;T

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.55

T;.

M_CAP

Benign

0.00083

MetaRNN

Benign

0.022

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

L;L

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Benign

0.022

Sift

Benign

0.12

T;T

Sift4G

Benign

0.13

T;T

Polyphen

0.081

B;B

Vest4

0.078

MutPred

0.63

Gain of solvent accessibility (P = 0.0037);Gain of solvent accessibility (P = 0.0037);

MVP

0.014

MPC

0.0026

ClinPred

0.016

GERP RS

-1.6

Varity_R

0.29

gMVP

0.0044

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over